scholarly journals Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-32 ◽  
Author(s):  
Patricia Marchio ◽  
Sol Guerra-Ojeda ◽  
José M. Vila ◽  
Martín Aldasoro ◽  
Victor M. Victor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Key Factors ◽  
Therapeutic Approaches ◽  
Inflammatory Chemokines ◽  
Atherosclerotic Process ◽  
Common Clinical Practice ◽  
Inflammatory Signalling

Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. Oxidation of low-density lipoprotein (LDL) cholesterol is one of the key factors for the development of atherosclerosis. Nonoxidized LDL have a low affinity for macrophages, so they are not themselves a risk factor. However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment. In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research.

scholarly journals Recognition of Oxidized Lipids by Macrophages and Its Role in Atherosclerosis Development

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 915
Author(s):  
Nataliya V. Mushenkova ◽  
Evgeny E. Bezsonov ◽  
Varvara A. Orekhova ◽  
Tatyana V. Popkova ◽  
Antonina V. Starodubova ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Formation Mechanisms ◽  
Therapeutic Approaches ◽  
Macrophage Response ◽  
New Therapeutic Approaches ◽  
Metabolic Imbalance ◽  
Atherosclerosis Development

Atherosclerosis is a multifactorial chronic disease that has a prominent inflammatory component. Currently, atherosclerosis is regarded as an active autoimmune process that involves both innate and adaptive immune pathways. One of the drivers of this process is the presence of modified low-density lipoprotein (LDL). For instance, lipoprotein oxidation leads to the formation of oxidation-specific epitopes (OSE) that can be recognized by the immune cells. Macrophage response to OSEs is recognized as a key trigger for initiation and a stimulator of progression of the inflammatory process in the arteries. At the same time, the role of oxidized LDL components is not limited to pro-inflammatory stimulation, but includes immunoregulatory effects that can have protective functions. It is, therefore, important to better understand the complexity of oxidized LDL effects in atherosclerosis in order to develop new therapeutic approaches to correct the inflammatory and metabolic imbalance associated with this disorder. In this review, we discuss the process of oxidized LDL formation, mechanisms of OSE recognition by macrophages and the role of these processes in atherosclerosis.

scholarly journals Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein

1997 ◽  
Vol 322 (1) ◽  
pp. 317-325 ◽  
Author(s):  
Jesús R. REQUENA ◽  
Min Xin FU ◽  
Mahtab U. AHMED ◽  
Alicia J. JENKINS ◽  
Timothy J. LYONS ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gas Chromatography ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Low Density ◽  
Lysine Residues

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(Nε-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(Nε-lysino)propane (LML)] and lysine-HNE [3-(Nε-lysino)-4-hydroxynonan-1-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70Ő80% of total lysine loss during the reaction with MDA. LM and LML (0.002Ő0.12mmol/mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

Differential PDGF secretion by graft and aortic SMC in response to oxidized LDL

2002 ◽  
Vol 283 (2) ◽  
pp. H725-H732 ◽  
Author(s):  
Afaf Absood ◽  
Akira Furutani ◽  
Tsutomu Kawamura ◽  
Linda M. Graham
Keyword(s):  
Oxidative Stress ◽  
Lipid Oxidation ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Vascular Grafts ◽  
Density Lipoprotein ◽  
Oxidation Products ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oxidized Low Density Lipoprotein ◽  
Lipid Oxidation Products

Smooth muscle cells (SMC) from prosthetic vascular grafts constitutively secrete higher levels of platelet-derived growth factor-AA (PDGF-AA) than aortic SMC. Lipid oxidation products accumulate in grafts and may stimulate PDGF production. The effect of oxidized low-density lipoprotein (oxLDL) on PDGF-AA secretion by aortic and graft SMC was compared. SMC isolated from canine thoracic aorta or Dacron thoracoabdominal grafts ( n = 10) were incubated with native LDL or oxLDL (0–400 μg/ml) for 72 h. PDGF-AA in the conditioned medium was measured with enzyme-linked immunosorbent assay. OxLDL increased PDGF-AA production by graft SMC from 78 ± 2 to 256 ± 16 pg PDGF/μg DNA and aortic SMC from 21 ± 1 to 40 ± 2 pg PDGF/μg DNA. Native LDL had no effect. N-acetylcysteine inhibited oxLDL-induced PDGF increase. Both superoxide and H2O2 stimulated PDGF secretion by graft SMC had little effect on aortic SMC. Our results suggest that PDGF production by graft (synthetic) SMC is more sensitive to stimulation by oxidative stress than aortic (contractile) SMC. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress, which stimulates PDGF production by graft SMC. PDGF can induce migration of aortic SMC onto the graft, contributing to the development of intimal hyperplasia.

scholarly journals Cross-Talk between Lipoproteins and Inflammation: The Role of Microvesicles

2019 ◽  
Vol 8 (12) ◽  
pp. 2059 ◽  
Author(s):  
Gemma Chiva-Blanch ◽  
Lina Badimon
Keyword(s):  
Plasma Membranes ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plaque Vulnerability ◽  
Therapeutic Approaches ◽  
Common Features ◽  
Cell Plasma ◽  
Novel Therapeutic

Atherothrombosis is the principal underlying cause of cardiovascular disease (CVD). Microvesicles (MV) are small blebs originated by an outward budding at the cell plasma membranes, which are released in normal conditions. However, MV release is increased in pathophysiologic conditions such as CVD. Low density lipoprotein (LDL) and MV contribute to atherothrombosis onset and progression by promoting inflammation and leukocyte recruitment to injured endothelium, as well as by increasing thrombosis and plaque vulnerability. Moreover, (oxidized)LDL induces MV release and vice-versa, perpetuating endothelium injury leading to CVD progression. Therefore, MV and lipoproteins exhibit common features, which should be considered in the interpretation of their respective roles in the pathophysiology of CVD. Understanding the pathways implicated in this process will aid in developing novel therapeutic approaches against atherothrombosis.

scholarly journals Oxidative Modification of LDL by Various Physicochemical Techniques: Its Probable Role in Diabetes Coupled with CVDs

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sultan Alouffi ◽  
Mohammad Faisal ◽  
Abdulrahman A. Alatar ◽  
Saheem Ahmad
Keyword(s):  
Oxidative Stress ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Physicochemical Analysis ◽  
The Body ◽  
Oxidative Modification ◽  
Oxidation Products ◽  
Set Up ◽  
Sera Samples

Background. Pro- and antiatherogenic properties of oxidised low density lipoprotein (Ox-LDL) are responsible for different chronic diseases including diabetes and cardiovascular diseases (CVD). The constant attack on the body from oxidative stress makes the quantification of various oxidation products necessary. In this study, the oxidative stress causing the structural and chemical changes occurring in the LDL molecule is comprehensively done. Moreover, the prevalence of the autoantibodies against the oxidised LDL is also determined. Methods. Our study made an attempt to see the effect of Ox-LDL as an enhancer of type 2 diabetes mellitus (T2DM) coupled with CVD. Primarily, we detected the oxidation of LDL with different concentration of Fenton reaction. The biochemical parameters were assessed for the changes occurring in the LDL molecule. In a clinical set up, 20 sera samples were taken from patients who are healthy, 30 from those with diabetes, 20 from those with CVD, and 30 from diabetes with CVD patients. Results. In biochemical assays there were markedly increased TBARS, carbonyl, and HMF content in Ox-LDL as compared to native LDL. The prevalence of autoantibodies against the T2DM was recorded to be 36%, while for CVD it was recorded to be 29%. However, it was found that 50% of the sera samples showed autoantibodies against oxidized LDL in the sera of T2DM with CVD complications as compared to the native analogue. Conclusion. There is significant change in the LDL molecule as revealed by various physicochemical analysis. The change in the LDL macromolecule as a result of oxidation triggered the development of the autoantibodies against it.

Melatonin Improves Lipid Profile and Ameliorates Lipid Peroxidation in Patients with Chronic Kidney Disease.

2018 ◽  
pp. 38-45
Keyword(s):  
Lipid Peroxidation ◽  
Placebo Group ◽  
Lipid Profile ◽  
Kidney Diseases ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Before And After ◽  
Inhibit Lipid Peroxidation ◽  
Controlled Clinical Study

Dyslipidemia and oxidative modifications of lipid are frequently associated in patients with chronic kidney diseases (CKD) and considered the most important risk factors for cardiovascular events. Melatonin is a well-known potent antioxidant and has beneficial effect on lipid metabolism. the study was designed to evaluate if Melatonin could improve lipid profile and ameliorates lipid peroxidation. This single blind placebo controlled clinical study carried out on 41 patients with CKD who were randomized into two groups, control groups (n=20) those who received placebo cap and melatonin group those who received 5mg melatonin (n=21). Lipid profile [total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C)] and parameters of lipid peroxidation [oxidized LDL (oxLDL) and malondialdehyde (MDA) were measured before and after 12 weeks of the treatment. After 12 weeks of treatment, melatonin significantly increased HDL-C and decreased LDL-C compared to the initial value. The elevation in HDL-C and reduction in LDL-C were significantly different from that in placebo group. Also, both oxLDL and MDA levels significantly lowered by melatonin compared to the baseline and to the placebo group. Collectively, the results of our study showed that melatonin has advantageous effect on lipid profile and inhibit lipid peroxidation in patients with CKD.

Effect of Turmeric and Ginger on Lipid Profile in Male Rats Exposed to Oxidative Stress

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Eman A. Al-Rekabi ◽  
Dheyaa K. Alomer ◽  
Rana Talib Al-Muswie ◽  
Khalid G. Al-Fartosi
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Drinking Water ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Male Rats ◽  
Control Group ◽  
Very Low Density Lipoprotein ◽  
Low Density

The present study aimed to investigate the effect of turmeric and ginger on lipid profile of male rats exposed to oxidative stress induced by hydrogen peroxide H2O2 at a concentration of 1% given with consumed drinking water to male rats. Methods: 200 mg/kg from turmeric and ginger were used, and the animals were treatment for 30 days. Results: the results showed a significant increase in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), whereas it explained a significant decrease in high density lipoprotein (HDL) of male rats exposed to oxidative stress when compared with control group. the results showed a significant decrease in cholesterol, triglycerides, (LDL), (VLDL), whereas it explained a significant increase in (HDL) of rats treated with turmeric and ginger at dose 200 mg/kg when compared with male rats exposed to oxidative stress.

Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

2019 ◽  
Vol 15 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Rabia Nabi ◽  
Sahir Sultan Alvi ◽  
Mohd. Saeed ◽  
Saheem Ahmad ◽  
Mohammad Salman Khan
Keyword(s):  
Oxidized Ldl ◽  
Advanced Glycation Endproducts ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Therapeutic Effects ◽  
Hmg Coa Reductase ◽  
Toxicological Effects ◽  
Coa Reductase

Introduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects. Objective: Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL by HMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesis via HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associated complications. Conclusion: Current article appraises the pathological AGE-RAGE concerns in diabetes and its associated complications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulating in tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing the potential protective role of HMG-R inhibitors against diabetic complications.

ClC-3: A Novel Promising Therapeutic Target for Atherosclerosis

2021 ◽  
pp. 107424842110236
Author(s):  
Dun Niu ◽  
Lanfang Li ◽  
Zhizhong Xie
Keyword(s):  
Therapeutic Target ◽  
Chloride Channels ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Molecular Structures ◽  
Foam Cell Formation ◽  
Endothelium Dysfunction ◽  
Atherosclerotic Process

Chloride channel 3 (ClC-3), a Cl−/H+ antiporter, has been well established as a member of volume-regulated chloride channels (VRCCs). ClC-3 may be a crucial mediator for activating inflammation-associated signaling pathways by regulating protein phosphorylation. A growing number of studies have indicated that ClC-3 overexpression plays a crucial role in mediating increased plasma low-density lipoprotein levels, vascular endothelium dysfunction, pro-inflammatory activation of macrophages, hyper-proliferation and hyper-migration of vascular smooth muscle cells (VSMCs), as well as oxidative stress and foam cell formation, which are the main factors responsible for atherosclerotic plaque formation in the arterial wall. In the present review, we summarize the molecular structures and classical functions of ClC-3. We further discuss its emerging role in the atherosclerotic process. In conclusion, we explore the potential role of ClC-3 as a therapeutic target for atherosclerosis.

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